Investigation of the Influence of Artificial Intelligence Markup Language-Based LINE ChatBot in Contextual English Learning.

This study is intended to create an innovative contextual English learning environment making use of the widely used communication software, LINE ChatBot, based on the Artificial Intelligence Markup Language (AIML), in order to improve speaking and listening ability among learners. A total of 73 students were invited to participate in learning activities involving a 4-week English conversation exercise including both speaking and listening. Additionally, in order to explore the influence of competition on language acquisition, we added competition characteristics to the learning activities in the experimental group to enhance learning motivation and learning outcomes. The results showed that with the help of the LINE ChatBot contextual learning environment, the performance of both groups of students was slightly enhanced, but no significant differences were found. Meanwhile, extrinsic motivation in both the experimental and control group was improved if they spoke anonymously. That is, the contextual learning environment based on the LINE ChatBot significantly improved the learners' English speaking and listening ability. In addition, the results showed that the addition of a competition element effectively enhanced the learners' intrinsic motivation to learn English on the LINE ChatBot.

An Immunobridging study to evaluate the neutralizing antibody titer in adults immunized with two doses of either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901.

BackgroundRapid development and deployment of vaccine is crucial to control the continuously evolving COVID-19 pandemic. Placebo-controlled phase 3 efficacy trial is still standard for authorizing vaccines in majority of the world. However, due to lack of cases or participants in parts of the world, this has not always been feasible. An alternative to efficacy trial is immunobridging, in which the immune response or correlates of protection of a vaccine candidate is compared against an approved vaccine. Here we describe a case study where our candidate vaccine, MVC-COV1901, has been granted for emergency use authorization (EUA) locally based on the non-inferiority immunobridging process. MethodsThe per protocol immunogenicity (PPI) subset from the MVC-COV1901 phase 2 trial was used for this study and consisted of 903 subjects who have received two doses of MVC-COV1901 as scheduled in the clinical trial. The comparator set of population consisted of 200 subjects of [≥] 20 years of age who were generally healthy and have received two doses of AstraZeneca ChAdOx nCOV-19 (AZD1222) recruited from Taoyuan General Hospital, Ministry of Health and Welfare. ResultsMVC-COV1901 was shown to have a geometric mean titer (GMT) ratio lower bound 95% confidence interval (CI) of 3.4 against the comparator vaccine and a seroconversion rate of 95.5% at the 95% CI lower bound, which both exceeded the criteria set by the Taiwan regulatory authority for EUA approval. These results supported the EUA approval of MVC-COV1901 by the Taiwanese regulatory authority in July 2021. Following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), countries from the Access Consortium has recently adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. ConclusionThe data presented in the study showed that it is reasonably likely that the vaccine efficacy of MVC-COV1901 is similar or superior to that of AZ. Data could be used in support of further vaccine development and regulatory approval.

Anti-spike antibody response to natural infection with SARS-CoV-2 and its activity against emerging variants

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially impacted human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2. Here, we demonstrated that acute SARS-CoV-2 infection elicits rapid and robust spike-binding and ACE2-blocking antibody responses, which wane approximately 11 months after infection. Serological responses were found to be correlated with the frequency of spike-specific memory B cell responses to natural infections. Further, significantly higher spike-binding, ACE2-blocking, and memory B cell responses were detected in patients with fever and pneumonia. Spike-specific antibody responses were found to be greatly affected by spike mutations in emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization. ImportanceAs spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined the spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Further, the serological responses were correlated with the frequency of spike-specific memory B cell responses to natural infections. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. Moreover, the spike-specific antibody responses were substantially affected by the emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Safety and immunogenicity of a heterologous booster of protein subunit vaccine MVC-COV1901 after two doses of adenoviral vector vaccine AZD1222

We report the interim safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 or 24 weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers were 14- and 8.6-fold increased, respectively, when compared to the titer levels on the day of the booster dose. We also observed 5.2- and 5.6-fold increases in neutralizing titer levels against wildtype and Omicron variant pseudovirus after the booster dose, respectively. These interim results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222.

Safety and Immunogenicity of SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901 in People Living with HIV

ObjectivesTo provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed. MethodsA total of 57 PWH of [≥] 20 years of age who are on stable antiretroviral therapy and with CD4+ T cell [≥] 350 cells/mm3 and HIV viral load < 103 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated. ResultsNo vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039). ConclusionsMVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-RBD, three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)

ObjectiveIn this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. MethodsSubjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. ResultsThere were 33 and 37 cases in the RCT and retrospective study, respctively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1-9 days) and 10 days (95% CI; 2-12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). ConclusionsNeither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6[A] crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.

Examination of well ordered nanonetwork materials by real- and reciprocal-space imaging.

The development of well ordered nanonetwork materials (in particular gyroid-structured materials) has been investigated using a block-copolymer template for templated electroless plating as an example system for the examination of network formation using X-ray scattering. By taking advantage of the nucleation and growth mechanism of templated electroless plating, gyroid-structured Au was successfully fabricated through the development of Au nanoparticles, then tripods and branched tripods, and finally an ordered network. Each stage in the development of the network phase could then be examined by combining real-space transmission electron microscopy observations with reciprocal-space small-angle X-ray scattering results. The fingerprint scattering profile of the building block for the network (i.e. the tripod of the gyroid) could be well fitted with the form factor of an effective sphere, and the diffraction results from the ordered network could thus be reasonably addressed. As a result, the examination of well ordered network materials can be simplified as the scattering from the form factor of a sphere convoluted with the nodes of its structure factor, providing a facile method of identifying the network phases from X-ray scattering data.

Fabrication of Mesoporous Polystyrene Films with Controlled Porosity and Pore Size by Solvent Annealing for Templated Syntheses.

Herein, we aim to develop a facile method for the fabrication of mesoporous polystyrene (PS) films with controlled porosity and pore size by solvent annealing. A PS polymer film is solvent-annealed using N,N-dimethyl formamide (DMF) vapor for the development of phase separation, followed by rapidly cooling to the preset cryogenic temperature. Subsequently, a nonsolvent (methanol) is introduced to extract the crystalline DMF from the DMF-swollen PS, giving mesoporous PS with a network structure after the removal of DMF. The porosity of the mesoporous PS films can be controlled by the degree of swelling. Most interestingly, the phase separation between PS and DMF at the thin-film state under solvent annealing can be regulated by the annealing time through the spinodal decomposition, giving the development of nanonetwork structure with controlled structural features (i.e., framework size and interframework spacing) at invariant porosity. Consequently, after the removal of DMF, mesoporous PS films with controlled porosity and pore size can be obtained and then used as a template for the fabrication of a variety of nanoporous inorganics by templated syntheses, such as nanoporous SiO2, TiO2, and Ni, providing a cost-effective way to fabricate a range of nanoporous materials with controlled porosity and pore size as well as large specific surface area for aimed applications.